This project is focused on translational clinical trials for the treatment of genitourinary malignancies (primarily prostate cancer). Currently five separate clinical trials are open and actively accruing patients.1. A Randomized Phase II Study of High Dose Ketoconazole plus Alendronate versus High Dose Ketoconazole in Patients with Androgen Independent Metastatic Prostate Cancer. This trial is designed to determine if the addition of alendronate to high dose ketoconazole produces acceptable disease responses as opposed to high dose ketoconazole alone. Translational end points are focused on the matrix metalloproteinase inhibition by alendronate. Forty patients have enrolled in this study.2. A Randomized Phase II Trial of Weekly Docetaxel Plus Thalidomide versus Weekly Docetaxel in Metastatic Androgen Independent Prostate Cancer Thalidomide and docetaxel have both shown biologic activity against androgen independent prostate cancer (AIPC). This is a randomized phase II study designed to evaluate the efficacy of weekly docetaxel as compared to the combination of docetaxel and thalidomide in patients with AIPC. Each patient that has biopsiable lesions undergo a pretreatment biopsy of their prostate (or other site of soft tissue disease). Molecular markers of apoptosis, angiogenesis as well as pharmacokinetics are evaluated in all patients. Thirty-six patients are enrolled in this study.3. A Double Blind Randomized Crossover Phase III Study of Oral Thalidomide versus Placebo in Patients with Stage D0 Androgen Dependent Prostate Cancer Following Limited Hormonal Ablation This randomized phase III study is designed to determine if thalidomide can prolong the break period in patients undergoing treatment with intermittent hormonal ablation for a biochemical recurrence of their prostate cancer. The effect of thalidomide on hormonal and angiogenic markers is evaluated during this trial. Eleven patients have enrolled on this study.4. A Randomized Phase II Study of Either Immunotherapy w/ a Regimen of Recombinant Pox Viruses that Express PSA/B7.1 + Adjuvant GM-CSF & IL-2 or Hormone Tx w/ Nilutamide in Patients w/ Hormone Refractory Prostate Ca & No Radiographic Evidence of Disease. This study compares the effectiveness of the drug nilutamide with that of an experimental vaccine in controlling advanced prostate cancer. Nilutamide (Nilandron) is an anti-androgen approved for treating prostate cancer. The vaccine is composed of the following parts:A) rV-PSA vaccinia virus plus human DNA that produces PSA (prostate specific antigen); B).rV-B7.1 vaccinia virus plus human DNA that produces B7.1 (a protein that helps guide immune cells to their targets);C) rF-PSA fowlpox virus plus human DNA that produces PSA; and D) GM-CSF and IL-2 drugs that boost the immune system. Patients that are A-2 positive have blood obtained to determine their immunologic response using the ELISPOT assay.5. A Randomized Phase II Study of a PSA-Based Vaccine in Patients with Localized Prostate Cancer Receiving Standard Radiotherapy. This study will test the ability of an experimental vaccine to stimulate the immune system of localized prostate cancer patients during radiation therapy. The vaccine is intended to stimulate lymphocytes to target and attack cells containing a protein called prostate specific antigen, or PSA. The vaccine is composed of the following parts:A) rV-PSA vaccinia virus plus human DNA that produces PSA (prostate specific antigen); B).rV-B7.1 vaccinia virus plus human DNA that produces B7.1 (a protein that helps guide immune cells to their targets);C) rF-PSA fowlpox virus plus human DNA that produces PSA; and D) GM-CSF and IL-2 drugs that boost the immune system. All patients have blood obtained to determine their immunologic response using the ELISPOT assay.